Dose Escalated Radiotherapy (RT) Alone or in Combination With Short-Term Total Androgen Suppression (TAS) for Intermediate Risk Prostate Cancer: Patient Reported Outcomes (PROs) From the NRG Oncology/RTOG 0815 Randomized Trial

Abstract

<h3>Purpose/Objective(s)</h3> To report the PROs of a phase III randomized trial evaluating TAS combined with dose-escalated RT for patients with intermediate risk prostate cancer. <h3>Materials/Methods</h3> Eligible patients had intermediate risk prostate cancer defined as harboring ≥ 1 of these risk factors: clinical stage T2b-T2c, Gleason score 7, or PSA > 10 to ≤ 20 ng/mL. Patients were randomized to dose-escalated RT alone (Arm 1) or RT plus TAS (Arm 2) consisting of LHRH agonist/antagonist with oral antiandrogen for 6 months. Validated PROs included the Expanded Prostate Cancer Index Composite (EPIC-50) and Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue short form. PRO change scores, calculated for each patient as the follow-up score minus baseline score (at end of RT, 6, 12, and 60 months from start of RT) were compared between treatment arms using a two-sample <i>t</i> test. An effect size (ES) of 0.50 SD (standard deviation) of the baseline measure was considered clinically meaningful. For the PRO sample size, 200 patients per arm would provide 90% statistical power to detect an ES < 0.50 if the completion rate was only 60%. Mixed effect regression models were also utilized. Clinical outcomes are reported in a separate abstract. <h3>Results</h3> Of the 402 initial planned subset of trial patients who completed baseline PROs, PRO compliance was approximately 96%, 89%, 86% and 87% at end of RT, 6, 12 and 60 months, respectively. There were no significant differences between these 402 patients and the remaining patients on this trial with respect to age, race, performance status, # risk factors, or comorbidity score. While EPIC urinary and bowel scores decreased significantly by the end of RT in both arms, no clinically meaningful differences between arms were detected over time. For the EPIC hormonal and sexual domains, however, there were clinically meaningful differences between the two arms with greater (<i>P</i> < 0.0001) deficits in the RT + TAS arm. These differences improved over time, with ∼50% resolution by one year after treatment and no clinically meaningful differences by 5 years between arms. PROMIS-fatigue scores increased from baseline in both arms and were significantly higher in arm 2 at the end of RT (<i>P</i> = 0.016), though slightly lower at 12 and 60 months. <h3>Conclusion</h3> The addition of TAS to dose-escalated RT demonstrated significant clinically meaningful declines in the EPIC hormonal and sexual domains, and increases in the PROMIS-fatigue scores, compared to RT alone. These scores gradually improved over time, with no clinically meaningful differences between arms in fatigue by one year, or in hormonal and sexual domains by 5 years. Beyond the clinical outcomes, these PRO results directly from patients provide added value to help patients make informed decisions among treatment options.